title: Oxygenated polyketides from Plakinastrella mamillaris as a new chemotype of PXR agonists.
abstract: Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K, together with the previously isolated gracilioethers E-G and gracilioethers I and J. The structure of the new compound has been elucidated by extensive NMR (1H and 13C, COSY, HSQC, HMBC, and ROESY) and ESI-MS analysis. With the exception of gracilioether F, all compounds are endowed with potent pregnane-X-receptor (PXR) agonistic activity and therefore represent a new chemotype of potential anti-inflammatory leads. Docking calculations suggested theoretical binding modes of the identified compounds, compatible with an agonistic activity on hPXR, and clarified the molecular basis of their biological activities.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", via D. Montesano 49, Naples 80131, Italy. angela.zampella@unina.it
authors.forename: Carmen
authors.initials: C
authors.lastname: Festa
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Amore
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Lauro
authors.forename: Simona
authors.initials: S
authors.lastname: De Marino
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: D'Auria
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Angela
authors.initials: A
authors.lastname: Zampella
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D001685:Biological Factors; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D061065:Polyketides / Q000737:chemistry* / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000819:agonists*
chemical_list: D000893:Anti-Inflammatory Agents; D001685:Biological Factors; D061065:Polyketides; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid